Edy Kornelius

DPP‐4 Inhibitor Linagliptin Attenuates Aβ‐induced Cytotoxicity through Activation of AMPK in Neuronal Cells

It is now clear that insulin signaling has important roles in regulation of neuronal functions in the brain. Dysregulation of brain insulin signaling has been linked to neurodegenerative disease, particularly Alzheimers disease (AD). In this regard, there is evidence that improvement of neuronal insulin signaling has neuroprotective activity against amyloid β (Aβ)‐induced neurotoxicity for patients with AD. Linagliptin is an inhibitor of dipeptidylpeptidase‐4 (DPP‐4), which improves impaired insulin secretion and insulin downstream signaling in the in peripheral tissues. However, whether the protective effects of linagliptin involved in Aβ‐mediated neurotoxicity have not yet been investigated.

Adherence to self-care behavior and glycemic effects using structured education

The purpose of the present study was to examine glycemic control in suboptimally controlled type 2 diabetes provided by a structured education group using the Diabetes Conversation Map™ (CM™) vs usual care in a university‐based hospital primary care clinic.

Iodinated Contrast Media Increased the Risk of Thyroid Dysfunction: A 6-Year Retrospective Cohort Study

CONTEXT The risks of thyroid dysfunction after iodinated contrast media (ICM) exposure are largely unknown, especially in Asian populations. OBJECTIVE The objective was to determine whether ICM exposure in patients with normal thyroid would increase the risk of thyroid dysfunction, including hyperthyroidism or hypothyroidism. DESIGN This was a retrospective cohort study including a random selection of 1 million people in 2005. SETTING General population of Taiwan was studied. PATIENTS Patients with ICM exposure were identified as cases, whereas patients without any ICM exposure were selected as controls. INTERVENTION Interventions included ICM exposure or nonexposure in normal thyroid function patients. MAIN OUTCOME The primary endpoint was the composite risk of thyroid dysfunction associated with ICM exposure. RESULTS A total of 19 642 cases and 78 568 matched controls were recruited in this study. The mean ages of ICM exposure and nonexposure were 53.9 and 53.6 years, respectively, and mean follow-up durations were 4.1 and 5.6 years, respectively. After adjustment, patients with ICM exposure had a significantly higher risk of thyroid dysfunction (hazard ratio, 1.46; 95% confidence interval [CI], 1.29-1.66). In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism and hypothyroidism compared with controls were 1.22 (95% CI, 1.04-1.44) and 2.00 (95% CI, 1.65-2.44), respectively. CONCLUSIONS ICM exposure was associated with higher risk of thyroid dysfunction, including hyperthyroidism and hypothyroidism.

Diabetes-related avoidable hospitalizations in Taiwan.

BACKGROUND An avoidable hospitalization (AH) is a condition that could have been prevented through effective treatment in outpatient care. Diabetes is often referred to as an ambulatory care-sensitive condition, and its associated hospitalizations are often referred to as avoidable hospitalizations. There are limited data on avoidable hospitalizations for individuals with diabetes in Taiwan. METHOD We used the National Health Interview Survey (NHIS) dataset to obtain diabetes-related avoidable hospitalizations for subjects aged above 12 years. We included data from 20,826 subjects who had completed the interview between 2004 and 2005. Data were collected from a total of 15,574 people, who had agreed to link their health information to the Taiwan National Health Insurance Research Database, including basic demographic variables, inpatient or outpatient medical events, admission date, discharge date, and diagnosis. The 1005 individuals who self-reported having diabetes or had at least 1 hospitalization or 2 physician service claims for diabetes mellitus with an ICD-9 diagnosis of 250 were included in the analysis. We divided those with diagnosis of diabetes into two groups: never hospitalized and hospitalized. The never hospitalized group served as the control group. We further identified hospitalized subjects with long-term complications due to diabetes (PQI-3) that included ICD-CM codes 250.4-250.9. RESULTS The mean ages of patients with diabetes-related long-term complications in the hospitalized and never hospitalized groups were 65 years and 58 years, respectively (p-value<0.01). More than half (52%) of the patients with diabetes-related long-term complications had a body mass index (BMI) lower than 24. The hospitalized group also had lower educational status compared with that of patients in the never hospitalized group (equal to or lower than elementary school, 63% vs. 50%; junior high school, 23% vs. 14%; equal or higher than senior high school, 14% vs. 36%). Furthermore, hospitalized patients tended to have lower household monthly income, were unmarried, and did not have private medical insurance. There were no significance differences in ethnic composition between the groups. Interestingly, patients with frequent retinal examination, and those with lower body mass index had higher frequency of avoidable hospitalization (p<0.01). CONCLUSION We found that the following factors were associated with a higher frequency of avoidable hospitalization among patients with type 2 diabetes: elderly, male, lower body mass index, lower household income, non-exercise, higher disease comorbidity, and frequent retinal examination.

Torsade de pointes—a rare presentation of primary hyperaldosteronism

Primary aldosteronism was the most common form of endocrine hypertension resulting in hypertension, metabolic alkalosis, and hypokalemia. Ventricular arrhythmia in association with primary hyperaldosteronism is an uncommon presentation that has previously been described in literature. We presented one case of torsades de pointes due to primary hyperaldosteronism.

Mevastatin promotes neuronal survival against Aβ-induced neurotoxicity through AMPK activation

Statins or HMG-CoA reductase inhibitors have been shown to be effective at lowering cholesterol levels, and the application of these molecules has gradually emerged as an attractive therapeutic strategy for neurodegenerative diseases. Epidemiological studies suggest that statin use is associated with a decreased incidence of Alzheimer’s disease (AD). Thus, statins may play a beneficial role in reducing amyloid β (Aβ) toxicity, the most relevant pathological feature and pathogenesis of AD. However, the precise mechanisms involved in statin-inhibited Aβ toxicity remain unclear. In the present study, we report that mevastatin significantly protects against Aβ-induced neurotoxicity in SK-N-MC neuronal cells by restoring impaired insulin signaling. This protection appears to be associated with the activation of AMP-activated protein kinase (AMPK), which has long been known to increase insulin sensitivity. Our results also indicate that high levels of cholesterol likely underlie Aβ-induced neurotoxicity and that activation of AMPK by mevastatin alleviates insulin resistance. Signaling through the insulin receptor substrate-1/Akt pathway appears to lead to cell survival. These findings demonstrate that mevastatin plays a potential therapeutic role in targeting Aβ-mediated neurotoxicity. The molecule presents a novel therapeutic strategy for further studies in AD prevention and therapeutics.

An Educational Intervention Using Steno Balance Cards to Improve Glycemic Control in Patients With Poorly Controlled Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is largely attributableto lifestyle factors. Although physiological and medical care needs must be met, psychosocial factors should not be neglected. Purpose: The aim of this study was to determine whether a 6-month intervention consisting of educational sessions using Steno Balance Cards, which involves guided group dialogue, resulted in better glycemic outcomes than conventional diabeteseducation. Methods: Patients with T2DM whose glycolated hemoglobin A1c levels were higher than 8% were recruited from September to October 2015. Ninety-two patients were assigned to either the psychosocial balance dialogue (PBD) group (n = 46) or the standard care (SC) group (n = 46). The PBD group received instructions about diabetes using the Steno “Balance Card” method, which involves the use of themed picture cards to elicit group dialogue. The Balance Cards were developed by the Danish Steno Diabetes Center. In the SC group, patients received general diabetes education using a conventional teachingmode. Results: In the PBD group, glycolated hemoglobin A1c decreased 1.3% from 8.1% ± 0.7% to 6.8% ± 0.8%, whereas it decreased 0.6% in the SC group from 8.0% ± 0.6% to 7.4% ± 0.7%, with p < .05. At the end of the 6-month study period, the PBD group and the SC group completed a health-related quality of life questionnaire(12-item Short-Form Health Survey) and a well-being index (WHO-5) questionnaire. In the PBD group, the difference before and after the intervention showed that the well-being (WHO-5) score increased by 45.4 points, whereas the physiological score increased by 28.0, and the mental component score increased by 29.0. In the SC group, the well-being (WHO-5) score increased by 6.4, whereas the physiological score increased by 4.7, and the mental component score increased by 9.6. There were statistically significant differences in questionnairescores between the two groups (p < .05). Conclusions/Implications for Practice: The results of this study indicate that the dialogue sessions using Steno Balance Cards are beneficial for patients with T2DM in terms of improved glycemic control and quality of life.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F β-cell apoptosis through restoration of PDX1 expression

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic β‐cells. Glucolipotoxicity‐mediated β‐cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse β‐cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining β‐cell function and survival, and glucolipotoxicity can activate mammalian sterile 20‐like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of β‐cells. Interestingly, previous research has demonstrated that increased glucagon‐like peptide‐1 (GLP‐1) signalling effectively protects β cells from glucolipotoxicity‐induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F β‐cells and demonstrate that the GLP‐1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating β‐cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect β‐cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.

THE TRENDS OF HYPERTHYROIDISM TREATMENT IN TAIWAN: A NATIONWIDE POPULATION-BASED STUDY

OBJECTIVE Few studies on hyperthyroidism treatment have been reported in the past 3 decades. We used a nationwide population-based database to evaluate the current practices and management of hyperthyroidism in Taiwan. METHODS This retrospective study included a random selection of 1 million people in Taiwan between 2004 and 2010. We identified patients with hyperthyroidism who received antithyroid drugs (ATD), radioactive iodine (RAI), or surgery. We calculated the proportions and treatment trends of those 3 treatment options annually. A Poisson regression model was used to determine whether trends changed. RESULTS The prevalence of overt hyperthyroidism in Taiwan steadily increased from 2,666 (0.27%) in 2004 to 3,464 (0.37%) in 2010. The incidence of hyperthyroidism (per 1,000 persons) also increased from 0.97 in 2004 to 1.06 in 2010. The major proportion of hyperthyroidism in this study was Graves disease (95%), followed by toxic nodular goiter (2%), and other causes (3%). ATD is the most commonly used (96-97%) treatment for hyperthyroidism, followed by surgery (2-3%) and RAI (<1%). There was a significant decreasing trend for surgery, from 2.9% in 2004 to 2% in 2010, especially in female patients (3.3% in 2004 to 2.3% in 2010, P<.01) and patients younger than 40 (3.8% in 2004 to 2.9% in 2010, P<.01). Meanwhile, the proportions of ATD and RAI remained unchanged. The most common ATD prescription was methimazole (45-50%), followed by propylthiouracil (30-32%) and carbimazole (19-21%). CONCLUSION Between 2004 and 2010, ATD was the treatment of choice in Taiwan, followed by surgery and RAI. ABBREVIATIONS ATA = American Thyroid Association; ATD = antithyroid drug; LHID2005 = Longitudinal Health Insurance database 2005 dataset; NHI = National Health Insurance; RAI = radioactive iodine.

Impact of potentially inappropriate medication and continuity of care in a sample of Taiwan elderly patients with diabetes mellitus who have also experienced heart failure

Continuity of care (COC) and potentially inappropriate medication (PIM) can affect the elderly healthcare outcome. We evaluated the COC and PIM effects in older diabetes mellitus (DM) patients with heart failure (HF).